Identifying noninvasive markers for Acute Cellular Rejection (ACR) has important implications for immunosuppressive management of transplant recipients. To date, diagnosing ACR is based on detecting biochemical evidence of graft dysfunction and the presence of suggestive allograft histology, including a lymphocytic infiltrate.(1,2) The presence of a cellular infiltrate and biochemical abnormalities, however, are not specific to ACR. For instance, the Hepatitis C virus (HCV) has similar clinical and histological effects, and distinguishing between the effects of HCV and ACR is difficult, especially because either or both events may occur simultaneously.
Conventional proteomic studies in kidney transplantation have focused on urine analysis. There are three urine proteomic analyses of acute rejection in renal transplant recipients,(14-16) ultimately identifying urinary beta 2-microglobulin and its fragments as potential biomarkers for ACR.(17) A single report, carried out in follow-up to a tissue proteomic analysis, found, using an ELISA method, that the abundance of alpha B-crystallin and tropomyosin are increased in serum during ACR in heart transplant recipients.(18) 
As therapeutic agents that inhibit rejection are associated with more severe infectious complications of transplantation, such as recurring HCV,(3-5) it seems likely that allograft injury due to infections and ACR are mechanistically distinct. ACR is characterized by antigen-triggered T-cell activation and the subsequent migration of activated CD4+ and CD8+ T-cells, macrophages and natural killer (NK) cells. As T-cell activation in ACR is characterized by a consistent and distinct motif of gene expression,(6) ACR is likely also associated with the expression of a subset of T-cell dependent immune activation proteins in serum.